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Sat August 2, 2014

Why Treating Ebola With An Experimental Serum Might Help

In 1995, amid an Ebola outbreak, Zairian Red Cross personnel picked up sick people and bodies left on the streets of Kikwit, 250 miles from the capital Kinshasa.

Jean-Marc BoujuAP

Last week we learned that two Americans working in Liberia for a medical charity, Samaritan's Purse, were among those who had contracted Ebola. When their symptoms took a turn for the worse, the organization announced that the two were going to get experimental treatments. One was going to get a blood transfusion from a 14-year-old boy who recovered from the disease, the organization said; the other was to get an "experimental serum." What's that?

We know there's no drug to treat Ebola (though several are in development). But sometimes the human body can mount a successful defense against this deadly virus. And 20 years ago, doctors adapted this natural defense to make an impromptu treatment during a previous Ebola outbreak.

The year was 1995. Ebola had erupted in the Democratic Republic of the Congo. Eighty percent of patients were dying. But a small group of doctors took blood samples from people who appeared to be on the road to recovery — and used that as an experimental treatment for other sick patients.

Here's the idea: A person who had managed to fight off the infection may have developed antibodies that circulate in the blood and that could neutralize the Ebola virus.

This isn't as crazy as it might seem. In fact, these "sera" were a common treatment for infectious diseases in the 19th century, before antibiotics came along. Sera are proven treatments for many infectious diseases, including diphtheria and botulism. In fact, the immune globulins used to treat tetanus today are a refined version of this process.

"For example, if you step on a nail and are exposed to tetanus, and you've never been vaccinated, you can get something called tetanus immune globulin, which works immediately," says Dr. E. Richard Stiehm, a pediatrics professor at the UCLA School of Medicine. These antibodies only stay in your body for about four weeks, he says, but that's often enough time to treat a sudden infection like Ebola.

And the source doesn't have to be other people — horses are also used to produce these antibodies for human drugs.

Because antibiotics are safer, sera fell out of favor starting in the 1940s for most diseases. And vaccines are a closely related concept — except that vaccines generally stimulate the body's immune system to produce its own antibodies, rather than transferring antibodies from somewhere else. Vaccines are much more effective because the antibodies are there at the time of infection. It's harder to knock down a disease that's already raging.

Still, if there's no drug, there's not much choice. Attempts to use sera against Ebola date back to 1977, just a year after the virus was first recognized as a threat to public health. But the technique relies on finding Ebola survivors who can donate their blood (and the antibodies it contains). So it's challenging even in the best of circumstances.

Stiehm and a pediatrician colleague from UCLA, Dr. Margaret Keller, note, in a published overview of the science, that goats were used to produce antibodies against Ebola in the early 1990s, and this serum "was then used in Russia for emergency prophylaxis for four patients exposed by laboratory accidents." Nobody got seriously ill, but it's not entirely clear what role the serum played in protecting them.

The most hopeful experience to date involves blood donors who were recovering from Ebola, back in Congo in 1995. Their blood was transfused into eight patients who were ill with Ebola. Normally 80 percent of people with Ebola die, but in this case, seven of the eight survived, according to a report by scientists from Congo and Belgium.

The medical charity Samaritan's Purse hasn't spelled out the source or the nature of the serum available to its workers.

These days, blood transfusions aren't the only possible source of sera. Researchers in Canada and Japan are currently developing custom-tailored antibodies to combat Ebola. These are "monoclonal" antibodies, meaning they are specifically designed to attack one thing — in this case, the Ebola virus. They've been successfully tested in monkeys, but it's not clear under what circumstances this material would be tested in humans.

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Transcript

MELISSA BLOCK, HOST:

Two American medical missionaries who contracted Ebola in Liberia received an experimental serum to treat the disease. That's according to the aid group they were working with, Samaritan's Purse. NPR's Richard Harris has this story about what serums are and their long and surprisingly successful history.

RICHARD HARRIS, BYLINE: When doctors talk about serum to treat disease, what they're talking about is antibodies taken from the bloodstream which can neutralize a specific germ. Dr. Arturo Casadevall at the Albert Einstein College of Medicine says, absent a proven drug to treat Ebola, serum is the next best thing.

ARTURO CASADEVALL: I think the idea makes perfect sense.

HARRIS: In fact, it has a rich history. Back in the late 19th century, doctors discovered that the blood taken from someone who had fought off a disease contains protective proteins called antibodies. The clear part of the blood - the serum - could be injected into somebody else, and the disease-fighting ability would be passed along.

CASADEVALL: And about 40 years, that was the only way to treat many infectious diseases. In those days, the serum is made in horses, and it was transferred to people. And it was used to treat pneumonia, meningitis and some other diseases, and it was very effective.

HARRIS: Antibiotics ended up replacing this treatment for most diseases, though they're still used in medicine today. Dr. E. Richard Stiehm is at the UCLA School of Medicine.

E. RICHARD STIEHM: For example, if you step on a nail and are exposed tetanus, and you've never been vaccinated, you can get something called tetanus immune globulin, which is antibodies from other people that work immediately.

HARRIS: There have been a few previous attempts to use this technique with Ebola. A study from 1995 reported on eight Ebola patients who had been given blood transfusions from people who had recovered from the disease. Seven of the eight survived.

CASADEVALL: But it's a now impractical thing because these patients that have convalesced from Ebola are very rare and hard to come by.

HARRIS: Instead, several labs around the world are at work using biotechnology to tailor-make anti-Ebola antibodies called monoclonal antibodies. That includes a Canadian government lab, a collaboration between the U.S. government and scientists in Japan and San Diego-based MAP BioPharmaceuticals. CNN was first to report that MAP BioPharmaceuticals provided the experimental serum that was used to treat the American missionaries who contracted Ebola. U.S. government officials later verified that report.

There are several scientific studies showing that monoclonal antibodies can protect monkeys from Ebola. And Casadevall says, success in animals is likely to mean success in people. But that's not to say this would work perfectly.

CASADEVALL: The thing about antibodies is that they work best if given before infection or shortly after infection. Often, when the disease has set in, antibodies are not that effective. But in some diseases, they are. And the only way to know whether, in fact, they would help individuals who are already ill would be to do the clinical trials.

HARRIS: Those human trials have not yet taken place, so it's not yet clear how well the monoclonal antibodies would work, either as treatment or prevention. Casadevall notes that there's a lot of skepticism of Western doctors in areas where Ebola is breaking out, so testing experimental drug would be a delicate matter.

CASADEVALL: You could imagine that it could initially be used on health care providers who are going to be going into these areas and be infected.

HARRIS: And if it proves useful for them, perhaps the affected population would be more receptive to trying this experimental therapy. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.